Potassium Carbonate → tert-Butyl 4-(2-((1-(5-propylpyrimidin-2-yl)piperidin-4-yl)methyl)benzo[d]oxazol-6-yl)-5,6-dihydropyridine-1 (2H)-carboxylate

HRID 1429548노트

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HRID 1429548 반응식
Br[C:2]1[CH:26]=[CH:25][C:5]2[N:6]=[C:7]([CH2:9][CH:10]3[CH2:15][CH2:14][N:13]([C:16]4[N:21]=[CH:20][C:19]([CH2:22][CH2:23][CH3:24])=[CH:18][N:17]=4)[CH2:12][CH2:11]3)[O:8][C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB([C:35]2[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH:36]=2)O1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.CCOC(C)=O.CCOCC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:22]([C:19]1[CH:18]=[N:17][C:16]([N:13]2[CH2:14][CH2:15][CH:10]([CH2:9][C:7]3[O:8][C:4]4[CH:3]=[C:2]([C:35]5[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH:36]=5)[CH:26]=[CH:25][C:5]=4[N:6]=3)[CH2:11][CH2:12]2)=[N:21][CH:20]=1)[CH2:23][CH3:24]

참가 물질

8

반응물 3

HCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 674649446-Bromo-2-((1-(5-propylpyrimidin-2-yl)piperidin-4-yl)methyl)benzo[d]oxazole

생성물 1

HCID 68208557tert-Butyl 4-(2-((1-(5-propylpyrimidin-2-yl)piperidin-4-yl)methyl)benzo[d]oxazol-6-yl)-5,6-dihydropyridine-1 (2H)-carboxylate수율 96.3%

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 312751,4-Dioxane용매HCID 21584169Diethylether ethylacetate용매

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온도
100 °C

실험 절차

To a degassed solution of 6-bromo-2-((1-(5-propylpyrimidin-2-yl)piperidin-4-yl)methyl)benzo[d]oxazole (0.15 g, 0.361 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (0.156 g, 0.506 mmol) and K2CO3 (0.125 g, 0.903 mmol) in dioxane (3.7 mL) and water (1.2 mL) was added Pd(Ph3P)4 (0.021 g, 0.018 mmol). The reaction mixture was stirred at 100° C. for 15 h. The reaction mixture was cooled to rt, and diluted with EtOAc/Ether (10 mL, 1:1 v/v). The organic layer was washed with NaHCO3 (aq, sat, 6 mL) and NaCl (saturated aqueous, 6 mL). It was dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 60% EtOAc) to afford desired product as a light yellow solid (180 mg, 96% yield). 1H NMR (400 MHz, chloroform-d) δ 8.14 (s, 2H), 7.61 (d, J=8.3 Hz, 1H), 7.47 (d, J=1.3 Hz, 1H), 7.38-7.33 (m, 1H), 6.15-5.95 (m, 2H), 4.73 (d, J=13.4 Hz, 1H), 4.10 (s, 2H), 3.67 (t, J=5.6 Hz, 3H), 2.99-2.79 (m, 3H), 2.57 (s, 2H), 2.46-2.33 (m, 2H), 2.32-2.13 (m, 2H), 1.87 (d, J=11.2 Hz, 2H), 1.63-1.53 (m, 1H), 1.50 (s, 9H), 1.37 (dd, J=12.5, 4.0 Hz, 2H), 0.93 (t, J=7.3 Hz, 3H). LCMS (m/z)=518 (M+H)+.

후처리

  1. temperatureThe reaction mixture was cooled to rt
  2. washThe organic layer was washed with NaHCO3 (aq, sat, 6 mL) and NaCl (saturated aqueous, 6 mL)
  3. dry with materialIt was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 60% EtOAc)

출처 및 근거

ORD 기록
ord-5b79b1b0f15d4a4b89f8e82fba541a47
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940716B2

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